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Biotech / Medical : Cell Therapeutics (CTIC) -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (193)	3/16/2004 3:47:49 AM
From: nigel bates	Read Replies (1) \| Respond to of 946

Arsenic Study May Point to Leukemia Treatments Mon Mar 15, WASHINGTON (Reuters) - A study of arsenic and leukemia showed why the old-fashioned, slow-acting poison sometimes works against cancer and may point to new treatments for leukemia, scientists said on Monday. A team at Johns Hopkins University in Baltimore found arsenic works in a similar way to bryostatin, a toxin made by coral-like sea animals that has been investigated as a possible cancer treatment. Put together, the two could offer a less toxic alternative to treating some forms of leukemia, the researchers said. Arsenic has been used for centuries in medicine. It is known to work against treatment-resistant acute promyelocytic leukemia or APL, a cancer of the blood and bone marrow that affects myeloid or white blood cells. APL is a subtype of acute myeloid leukemia, the most common form of adult leukemia. Dr. Chi Dang and colleagues said they set out to find how arsenic works. Working in lab dishes, the Johns Hopkins team found that arsenic targets an oxygen-producing enzyme complex known as NADPH oxidase. "When normal white blood cells engulf invading bacteria, NADPH oxidase produces a big burst of bad oxygen species (charged molecules of oxygen) which they dump into bacteria to kill it and, in the process, kill themselves," Dang said in a statement. "We found that in APL, arsenic triggers activation of NADPH oxidase and uses this natural bacteria-killing mechanism against the leukemia cells -- in essence, a self-destruct switch." But arsenic cannot activate this mechanism fully enough to kill the cancer on its own, Dang said. "Even with arsenic treatment, much of the NADPH oxidase remains dormant in our system," Dang said. His team knew that bryostatin also activated NADPH oxidase, "so, we used bryostatin to wake up the rest of it," he said. They could kill tumor cells with one-tenth the usual dose of either drug given alone, they found. That could mean a less toxic cancer treatment, said Dr. Wen-Chien Chou, who also worked on the study. "Arsenic is similar to other chemotherapeutic agents in terms of its potential toxicity, and there's a trade-off in how much harm you do to normal cells versus cancer cells," Chou said. "Yet, the synergistic effects of combining two drugs that activate the same pathway may allow us avoid toxicity using such low doses."

To: Icebrg who wrote (193)	4/7/2004 7:50:13 AM
From: Thai Chung	Read Replies (1) \| Respond to of 946

Arsenic Trioxide in Combination with All-Trans Retinoic Acid (ATRA) Yields High Quality Remission and Survival in Newly Diagnosed Acute Promyelocytic Leukemia (APL) Wednesday April 7, 7:00 am ET First Non-Anthracycline Containing Induction Regimen for Treating Acute Leukemia Provides Basis for Potential Label Expansion Trials for TRISENOX(R) SEATTLE, April 7 /PRNewswire-FirstCall/ -- A study by Zhu Chen of the Shanghai Institute of Hematology and an international group from the University of Paris and the Mount Sinai School of Medicine in New York published in the April 2004 edition of the Proceedings of the National Academy of Sciences (PNAS), concluded that the combination of arsenic trioxide and ATRA induction therapy resulted in faster time to achieve complete remission (CR) and longer lasting remissions than either of the two drugs used alone. Sixty-one newly diagnosed APL patients were randomized into three treatment groups; single agent ATRA, single agent arsenic trioxide, or the combination of the two. Though CR rates in all groups were high (>90%), the leukemia burden at time of CR decreased more significantly in the combined therapy group compared to the mono-therapy arms. Importantly, all 20 cases in the combination group remained in CR after a median follow up of 18 months, whereas, seven of the 37 patients (19 percent) treated with mono-therapy relapsed. Studies at the molecular level demonstrated that the combination was 17.7 times more effective at eliminating leukemic cells than with ATRA alone and 3.7 times more effective than with arsenic trioxide alone. Cell Therapeutics, Inc. (CTI) (Nasdaq: CTIC; Nuovo Mercato) markets TRISENOX (arsenic trioxide) injection in the United States and Europe. "Standard induction treatment for front line APL currently consists of ATRA plus an anthracycline chemotherapy which results in a high rate of remission and cure. While very effective in eradicating this particular leukemia, anthracyclines are unfortunately associated with substantial short-term toxicities including hair loss, neutropenia, infections and mucositis. More importantly, for the large proportion of APL patients that are cured, the large doses of anthracyclines used are associated with an increased lifetime risk for developing secondary leukemias and myelodysplastic syndromes and may cause permanent impairment in heart function," explained Jack W. Singer, MD and Chief Medical Officer at CTI. "Given the preliminary experience of this study, we're moving quickly to conduct our own clinical trial to determine if TRISENOX can replace the requirement for an anthracycline in the induction treatment of patients with newly diagnosed APL." To view the PNAS report, please see the following link: pnas.org